title: Osteonecrosis of the jaw and oral health-related quality of life after adjuvant zoledronic acid: an adjuvant zoledronic acid to reduce recurrence trial subprotocol (BIG01/04).
abstract: OBJECTIVE
  In patients with early breast cancer, adjuvant zoledronic acid (zoledronate) may reduce recurrence and improve survival. However, zoledronate is associated with the occasional development of osteonecrosis of the jaw (ONJ). We report on the frequency of ONJ and investigate oral health-related quality of life (Oral-QoL) in a large randomized trial (Adjuvant Zoledronic Acid to Reduce Recurrence [AZURE]).
  
  
  METHODS
  Three thousand three hundred sixty women with stage II or III breast cancer were randomly assigned to receive standard adjuvant systemic therapy alone or with zoledronate administered at a dose of 4 mg for 19 doses over 5 years. All potential occurrences of ONJ were reported as serious adverse events and centrally reviewed. Additionally, we invited 486 study participants to complete the Oral Health Impact Profile-14 (OHIP-14) to assess Oral-QoL around the time the patients completed 5 years on study. Multivariable linear regression was used to calculate mean scores and 95% CIs in addition to identifying independent prognostic factors.
  
  
  RESULTS
  With a median follow-up time of 73.9 months (interquartile range, 60.7 to 84.2 months), 33 possible cases of ONJ were reported, all in the zoledronate-treated patients. Twenty-six cases were confirmed as being consistent with a diagnosis of ONJ, representing a cumulative incidence of 2.1% (95% CI, 0.9% to 3.3%) in the zoledronate arm. Three hundred sixty-two patients (74%) returned the OHIP-14 questionnaire. Neither the prevalence nor severity of impacts on Oral-QoL differed significantly between zoledronate patients and control patients.
  
  
  CONCLUSIONS
  Adjuvant zoledronate used in the intensive schedule studied in the AZURE trial is associated with a low incidence of ONJ but does not seem to adversely affect Oral-QoL.
authors.affiliation: Academic Unit of Clinical Oncology, Weston Park Hospital, Sheffield, S10 2SJ, England.
authors.forename: Emma J
authors.initials: EJ
authors.lastname: Rathbone
authors.forename: Janet E
authors.initials: JE
authors.lastname: Brown
authors.forename: Helen C
authors.initials: HC
authors.lastname: Marshall
authors.forename: Michelle
authors.initials: M
authors.lastname: Collinson
authors.forename: Victoria
authors.initials: V
authors.lastname: Liversedge
authors.forename: Geraldine A
authors.initials: GA
authors.lastname: Murden
authors.forename: David
authors.initials: D
authors.lastname: Cameron
authors.forename: Richard
authors.initials: R
authors.lastname: Bell
authors.forename: Saiqa
authors.initials: S
authors.lastname: Spensley
authors.forename: Rajiv
authors.initials: R
authors.lastname: Agrawal
authors.forename: Rema
authors.initials: R
authors.lastname: Jyothirmayi
authors.forename: Prabir
authors.initials: P
authors.lastname: Chakraborti
authors.forename: Frances
authors.initials: F
authors.lastname: Yuille
authors.forename: Robert E
authors.initials: RE
authors.lastname: Coleman
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000009:adverse effects; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D004164:Diphosphonates / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects*; D007571:Jaw Diseases / Q000139:chemically induced* / Q000188:drug therapy; D008875:Middle Aged; D009909:Oral Health; D010020:Osteonecrosis / Q000139:chemically induced* / Q000188:drug therapy; D011788:Quality of Life; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid